Microneedles Revolutionizing Diabetic Wound Healing
Diabetic wounds pose a significant health risk, often leading to severe complications such as amputations. These persistent, non-healing wounds are characterized by chronic inflammation and impact over six percent of the global population.
In Singapore alone, an estimated four lower limb amputations occur daily due to non-healing diabetic wounds. A study on diabetic wounds in Singapore reported that the average healthcare cost associated with amputation per patient was approximately S$23,000 in 2017.
To address this critical global and national health challenge, researchers at the National University of Singapore (NUS) have developed two innovative microneedle-based technologies. These cutting-edge solutions have demonstrated effectiveness in expediting diabetic wound healing in preclinical studies by preserving the function of essential growth factors and eliminating harmful inflammatory compounds.
The breakthrough technologies were pioneered by a research team led by Assistant Professor Andy Tay from the Department of Biomedical Engineering at the College of Design and Engineering, NUS, in collaboration with the Institute for Health Innovation and Technology. “We aimed to leverage microneedles for both therapeutic delivery and extraction. This approach is minimally invasive, enables precise fabrication, and facilitates painless direct administration of active compounds into wounds. Microneedle patches offer significant advantages for wound healing,” he stated.
The findings from these studies were published in two esteemed scientific journals—Biomaterials on July 4, 2024, and Advanced Functional Materials on July 24, 2024—highlighting the potential of these technologies for treating various skin conditions, including psoriasis and chronic diabetic wounds.
Innovative Strategies for Accelerating Wound Healing
Currently, hydrogel-based delivery systems are commonly used to administer growth factors to wounds. However, these methods are not very effective, as the high levels of proteases in chronic wounds rapidly degrade and neutralize growth factors. Consequently, high-dose and repeated applications are necessary, making the treatment expensive and inefficient.
The first innovation by the NUS team enhances the natural production of growth factors within the wound, rather than delivering them externally. To achieve this, the researchers developed sucralfate microneedles (SUC-MN) designed to deliver interleukin-4 (IL-4), a key immunomodulatory protein that stimulates the body’s own production of growth factors in diabetic tissues. IL-4 plays a crucial role in immune regulation and tissue regeneration, while sucralfate—a drug traditionally used for treating gastrointestinal ulcers—protects these growth factors from degradation.
Upon application, the microneedles dissolve within the wound, ensuring localized IL-4 and sucralfate delivery. This method reduces systemic side effects and prevents secondary damage often caused by conventional adhesive dressings. Experimental results indicate that SUC-MN enhances wound healing twice as fast compared to traditional treatments.
First-of-its-Kind Extractive Microneedles for Inflammation Control
While most microneedle technologies focus on delivering therapeutic agents, the NUS team explored a novel concept: using microneedles to extract harmful pro-inflammatory compounds.
To implement this approach, the researchers sought a suitable coating material capable of absorbing chemokines—messenger molecules that attract and retain inflammatory immune cells (monocytes) in wound tissues. Following extensive screening, the team identified heparin-coated porous microneedles (HPMN) as an optimal solution for mitigating persistent inflammation.
Heparin has demonstrated strong binding capabilities with chemokines in previous studies. The NUS team found that HPMN could effectively remove chemokines and monocytes from wound sites, resulting in a 50% reduction in tissue inflammation and a 90% decrease in wound size within 14 days of treatment.
These groundbreaking findings underscore the potential of HPMN in treating inflammatory skin disorders. Unlike existing treatments that primarily address surface-level inflammation, HPMN penetrates deeper into the skin, offering a more comprehensive therapeutic effect. This technology holds promise for personalized wound care and targeted treatments for conditions like psoriasis.
Future Directions
The introduction of SUC-MN and HPMN marks a significant advancement in wound healing and dermatological treatments. Moving forward, the NUS team plans to conduct additional studies to further refine and commercialize these technologies.
For extractive microneedles, researchers aim to optimize the pore size using advanced techniques like 3D printing and incorporate antibacterial properties, given the high risk of infections in chronic wounds. Additionally, they are designing flexible microneedle patches that can conform to various wound shapes for enhanced application.
“We are thrilled by the potential impact of our research and are committed to advancing this technology towards clinical application. Our dual approach provides much-needed solutions for diabetic wound patients and individuals suffering from skin conditions such as atopic dermatitis and psoriasis,” said Asst Prof Tay.
